We previously reported on the relationship of body composition and radiographic knee osteoarthritis development by analyzing longitudinal data acquired from the participants of the Baltimore Longitudinal Study on Aging (BLSA). Body composition data (fat and lean mass) acquired from 593 dual photon xray absorptiometry (DXA) scans of BLSA participants who had no evidence of knee osteoarthritis (OA) on an initial knee radiograph and underwent a second xray 10 years later. Body weight, and the ratios of fat to lean mass (60.97 versus 51.03 kg; p < 0.01) and fat mass to body weight (36.52 versus 32.43 kg; p < 0.001) were significantly higher in the 41 participants who went on to develop knee OA than those who remained free of radiographic disease in the 10 year observation period. We conducted further analyses to determine whether weight loss reduced the risk of knee OA development in the BLSA cohort. Interestingly, weight loss reduced the risk of knee OA development in men but not in women. We also examined the relationship between bone mineral density (BMD) and knee (OA) in this sample of volunteers. Data from 230 BLSA participants with OA were compared to the 211 who remained free of KOA over a 10-year follow-up interval. Taking age, gender, body mass index (BMI) and time interval between studies into account, BMD was higher with in younger subjects with more advanced OA, and lower in older subjects with advanced OA. The results of these analyses emphasize the complexity of the relationship between OA, body fatness and bone density and underscore the importance of taking age and gender into account. We will be conducting a study to investigate inflammatory, metabolic and hormonal factors mediators of the above reported relationships between body composition (body fatness and bone mineral density) and knee osteoarthritis development, and also to determine these factors respond to weight loss and physical activity. Testing of samples of serum and urine have been retrieved from storage and will commence shortly.